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Rothwell PM.

Large pragmatic trials provide the most reliable data about the effects of treatments, but should be designed, analysed, and reported to enable the most effective use of treatments in routine practice. Subgroup analyses are important if there are potentially large differences between groups in the risk of a poor outcome with or without treatment, if there is potential heterogeneity of treatment effect in relation to pathophysiology, if there are practical questions about when to treat, or if there are doubts about benefit in specific groups, such as elderly people, which are leading to potentially inappropriate undertreatment. Analyses must be predefined, carefully justified, and limited to a few clinically important questions, and post-hoc observations should be treated with scepticism irrespective of their statistical significance. If important subgroup effects are anticipated, trials should either be powered to detect them reliably or pooled analyses of several trials should be undertaken. Formal rules for the planning, analysis, and reporting of subgroup analyses are proposed.